The objectives of this research are: (1) to develop highly sensitive serologic assays for DNA base damage, (2) to apply the assays to the study of cellular damage and its repair, and (3) to study the relation of base damage to carcinogenesis and mutagenesis. The serologic approach is important since current physical-chemical methods for the study of base damage at low doses and within the DNA macromolecule are inadequate. Serologic assays are highly sensitive and specific and permit quantitation of particular ionizing radiation damaged bases. Assay systems are being developed for quantitation of products in isolated DNA and for localization within cell preparations. Antibodies have been prepared to the ionizing radiation products. 5 hydroxymethyluridine, and 8,5' cycloadenosine and by phage neutralization assay, yields have been measured in irradiated solutions of parent compounds under several conditions. Both products have been detected in irradiated DNA. We have developed a radioimmune assay for UV photoproducts and production and repair of damage in HeLa cells has been followed. Antibodies hve been prepared to 06 ethylguanosine and a highly sensitive method for the detection of this product in ethylnitrosourea treated DNA has been developed. Repair studies will be extended to include ionizing radiation and chemical carcinogen damaged bases. Damage accumulation and repair will be correlated with survival and mutagenesis in cell systems.